ARTICLE: Clinical Insights About the Role of pH in Acne

December 2019 | Volume 18 | Issue 12 | Supplement Individual Articles | 221 | Copyright © December 2019

Charles Lynde MD FRCPC

American Board of Dermatology, Royal College of Physicians and Surgeons of Canada, Department of Medicine, University of Toronto, Toronto, ON, Canada, Lynderm Research, Markham, ON, Canada 

Jerry Tan MD FRCPC

Royal College of Physicians and Surgeons of Canada, Schulich School of Medicine and Dentistry, Department of Medicine, Western University, Windsor, ON, Canada, Windsor Clinical Research Inc., The Healthy Image Centre, Windsor, ON, Canada Sandra Skotnicki MD FRCPC

American Board of Dermatology, the Royal College of Physicians and Surgeons of Canada, Department of Medicine, Divisions of Dermatology, and Occupational and Environmental Health, University of Toronto, Toronto, ON, Canada, Bay Dermatology Centre, Toronto, ON, Canada Anneke Andriessen PhD

Radboud UMC, Nijmegen and Andriessen Consultants, Malden, The Netherlands 

Jennifer Beecker MD CCFP(EM) FRCPC DABD

Royal College of Physicians and Surgeons of Canada, American Board of Dermatology, University of Ottawa, Ottawa, ON, Canada, The Ottawa Hospital, Director of Research, The Ottawa Hospital Research Institute, Ottawa, ON, Canada 

Joël Claveau MD FRCPC

American Board of Dermatology, Royal College of Physicians and Surgeons of Canada, Department of Medicine, Laval University, Quebec City, QC, Canada; Melanoma and Skin Clinic, Le Centre Hospitalier Universitaire de Québec, Hôtel-Dieu de Québec, Quebec City, QC, Canada 

Monica K. Li MD FRCPC

Royal College of Physicians and Surgeons of Canada, Faculty of Medicine, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada, Enverus Medical, Surrey, BC, Canada and Cosmetic Dermatologist, City Medical Aesthetics Center, Vancouver, BC, Canada 

Jaggi Rao MD FRCPC

Royal College of Physicians and Surgeons of Canada, Division of Dermatology, University of Alberta, Edmonton, AB, Canada 

Jennifer Salsberg MD FRCP

Royal College of Physicians and Surgeons of Canada, University of Toronto, Women’s College Hospital, Toronto, ON, Canada, Bay Dermatology Centre, Toronto, ON, Canada Maxwell B. Sauder MD FRCPC FAAD

Royal College of Physicians and Surgeons of Canada, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA, Harvard Medical School, Boston, MA, Toronto Dermatology Centre, Toronto, ON, Canada 

Catherine Zip MD FRCPC

Royal College of Physicians and Surgeons of Canada, Department of Medicine, University of Calgary, Calgary, AB, Canada, Dermatologist, Dermatology Centre, Calgary, AB, Canada

Statement 1: Acne is a common inflammatory skin disorder, which is multifactorial.

The concept of four contributing factors of sebaceous hyperexcretion– follicular hyperkeratinization, Cutibacterium acnes (C. acnes), Propionibacterium granulosum (P. granulosum) colonization, and inflammation is now considered too simple.5,8 Current thought is that acne lesions develop with a pattern of innate inflammation,8 which is triggered by direct and indirect multifactorial, complex, and interrelated mechanisms. These mechanisms include generation of chemotactic and proinflammatory factors such as activation of toll-like receptors (TLR), interleukin 1 (IL) and IL-8, human β-defensin (hBD) 1 and 4, and matrix metalloproteases (MMPs), all of which stimulate inflammatory mediators.5,6,8 Early cascades of the inflammatory response progress into inflammatory patterns involved in acne lesion formation up to and including scar formation in some patients.8

Statement 2: Factors involved in acne pathogenesis include inflammation, sebum hyperexcretion, follicular hyperkeratinization, Cutibacterium acnes, androgenic hormones, and skin barrier defect.

In acne-affected skin, sebaceous hyperexcretion and follicular hyperkeratinization are influenced by changes in the hormonal milieu including elevated insulin, IGF-1, and androgen levels.5,6,8,9 These elevated levels lead to disinhibition of transcription factor Fox01 and activation of mTORC1, which is nutrient sensitive and triggers cell growth and proliferation. These cascades result in increased local pilosebaceous androgenesis, lipogenesis, and increased squalene, fatty acid production, and desaturation.6,9 The elevated sebum production activates the proliferation of P. acnes (formerly called C. acnes), which together with IL-1β upregulation and subsequent adaptive immune response generate inflammatory acne lesions.6,9,10 In these inflammatory acne lesions, matrix metalloproteinases, including β-defensin 4, IL-1, IL-8, and granulysin are upregulated.6,9,11

Sebum Hyperexcretion
Sebaceous glands produce and excrete sebum together with lipids from epidermal layers, including triglycerides and fatty acid breakdown products, wax esters, squalene, cholesterol esters, and cholesterol.6,9 Sebum helps maintain the moisture content on skin and a physiological skin surface pH, and protects the skin from sunlight, bacterial infection, and from friction.12-14 In order to maintain a healthy skin condition, the composition of skin lipids is also crucial. Low levels of essential fatty acid and linoleic acid have been observed in skin surface lipids of acneaffected skin.6,9 Additionally, elevated sebum production favors the proliferation of C. acnes and the attendant lipase catalysis of triglycerides to free fatty acids, palmitic, and oleic acid, all of which leads to inflammasome activation.6,9 Together with IL-1β, upregulation, and the subsequent adaptive immune response activation, inflammatory papules, pustules, and nodules are formed.5,6,8,9

Follicular Hyperkeratinization
An ongoing debate exists as to whether hyperkeratinization of the follicular duct precedes the influx of inflammatory cells in acne or vice versa.6,8,9 Studies support an increase in IL-1 activity occurring before hyperproliferation around uninvolved follicles, thus triggering activation of keratinocytes.6,9,11 In fact, upregulated levels of IL-1 are also found in uninvolved skin of patients with acne.11 This cytokine may be an important trigger for cutaneous inflammation, with the resultant keratinocyte proliferation leading to the transformation of a normal follicle into an acne lesion.15

Cutibacterium acnes (C. acnes)
Biochemical and genomic investigations have led to the new taxonomic classification of P. acnes to be renamed Cutibacterium acnes (C. acnes).5 The gram‐positive anaerobic bacterium C. acnes is a dominant resident in the sebaceous follicles. While the contribution of C. acnes to acne development is unclear, its protective role as a commensal bacterium of healthy skin microbiota has been confirmed.10 Due to its metabolic features C. acnes is able to colonize the lipid‐rich sebaceous follicles, playing a role in maintaining equilibrium of the skin’s microbiome. 5,10,11 C. acnes can degrade triglycerides present in sebum to generate short‐chain fatty acids, including propionic acid, the accumulation of which adds to the continuation of an acid skin pH.5,10

Certain phylotypes have been demonstrated to be proinflammatory and associated with acne, and others have been shown to be the reverse. In acne-affected skin, C. acnes and its different phylotypes may contribute to the virulence and the antimicrobial resistance of acne‐associated strains.5,10,15 Further research should be conducted to explore how the seemingly harmless C. acnes may have a pathogenic effect on the development of acne lesions. Moreover, to what extent an elevated skin surface pH influences acne lesion development also needs to be investigated.5,15

Androgenic Hormones
Hormonal changes are the driving mechanism that triggers elevated sebum formation and C. acnes, thereby decreasing skin microbial diversity.5 Androgens such as testosterone and dihydrotestosterone (DHT), implicated in acne pathogenesis, are crucial for regulating sebum production.12-14 Individuals with acne-prone skin have larger-sized sebaceous glands that are stimulated at the time of puberty.13 DHT is shown to be more selective to sebocytes of the face but not of the leg13; this selectivity determines